Epidemiology of human papillomavirus on anogenital warts in Portugal - The HERCOLES study.

BACKGROUND: Anogenital warts (AGW) are one of the most prevalent sexually transmitted disease worldwide. Approximately, 90% of AGWs are related to infection by HPV 6 and 11. However, AGW have been associated with infection by multiple genotypes, including HR-HPV, which may be associated with a long-term increased risk of anogenital cancer. OBJECTIVE: This observational prospective epidemiological study aims to estimate the type-specific HPV distribution on incident AGWs in both genders, and additionally to assess the frequency of anal and oral HPV infection in patients with AGWs. METHODS: According to defined inclusion criteria, individuals with incident clinical diagnosis of AGWs were recruited in seven Portuguese Centres. HPV genotyping was performed using CLART HPV2 test. RESULTS: Between November 2012 and March 2014, 162 women and 400 men (mean age: 34 years), were enrolled. After exclusion of patients with unqualified AGW samples, HPV was detected in 95.3% (505/530) AGW patients, 96.8% males and 91.6% females. Among men who have sex with men, HPV was detected in 98.5% patients. HPV 6 and/or HPV 11 were the most frequent genotypes (87.5%), and HPV 16 the most common HR-HPV (9.2%). Infection with HPV 6/11 and any HR-HPV was observed in 35.8% patients. HPV prevalence on the anal canal and oral mucosa was 83.1% and 15.0%, respectively. CONCLUSION: Incident AGWs were more frequent in males than in females. LR-HPVs were more common among males and HR-HPVs among females. HPV 6 and 11 were the most common genotypes on both genders. However, there was also a high prevalence of HR-HPVs, particularly of HPV 16. AGWs represent a clinical marker of both anal and oral HPV infections, including anal HR-HPV infections in women and men who have sex with men. The HERCOLES study could be a clue to further investigations concerning HPV burden of disease by gender and sexual behaviour.

Prognostic value of human papillomavirus types 16 and 18 DNA physical status in cervical intraepithelial neoplasia.

The aim of this work was to assess the value of the physical status of human papillomavirus (HPV) DNA as a disease marker for cervical cancer development in a set of 248 DNA samples previously genotyped as HPV 16 or 18, by calculating the E2/E6 ratio through real-time PCR. There was a significant difference in integration status according to disease grade for both genotypes (p <0.001). Furthermore, especially for HPV 18, determining the DNA physical status could be a useful biomarker in predicting cervical cancer risk development, with a lower E2/E6 ratio clinically associated with the development of a precancerous lesion.

Single and multiple human papillomavirus infections in cervical abnormalities in Portuguese women.

Persistent infection with high-risk (HR) human papillomavirus (HPV) types is necessary for cervical cancer development. However, little is known about the influence of multiple HPV infections on cervical lesion risk. The aim of this study was to evaluate the frequency of single and multiple HPV infections in Portuguese women, and to assess the frequency of multiple infections in cervical intraepithelial neoplasia (CIN). HPV prevalence, type-specific prevalence and extent of multiple infections were assessed in 1057 cervical samples. The Clinical Array HPV assay was used to detect 35 HPV types. According to histological diagnosis, 425 samples were normal, 375 were CIN1, and 257 were CIN2+. HPV status was studied in relation to age and lesion severity. The prevalence of HPV infection was 52.7%; 25.4%, 67.2% and 76.7% were positive for any HPV type in the normal, CIN1 and CIN2+ cases, respectively. Among HPV-positive cases, 32.0% were associated with multiple infections. Among multiple infections, 96.1% harboured HR HPV types and 38.2% HR-low risk (LR) HPV types. Overall, 33 different HPV types (18 HR and 15 LR) were detected. HR HPV types (44.1%) were significantly more prevalent than LR HPV types (8.6%). The most frequent genotype was HPV 16 (25.5%), followed by HPV 31, 53, 66, 58, and 51. Multiple infections showed a significant increase (p 0.005) according to severity of neoplasia, particularly for HR-HR HPV infections (p 0.003). No association between age and multiple HPV infections was observed (p 0.812). However, multiple HR HPV infections were more frequent in women under 30 years of age (35.3%).

Molecular epidemiology of hepatitis A virus in a group of Portuguese citizens living in Lisbon area.

Hepatitis A virus (HAV) is the most important cause of acute infectious hepatitis worldwide. In Portugal, due to improvements in sanitation epidemic outbreaks of HAV infection have become less frequent. This report is the first, to our knowledge that characterized HAV in Portugal. For the detection and molecular characterization of HAV cases in a group of Portuguese individuals in the Lisbon area, 31 serum samples were tested: 8 from symptomatic children from an acute hepatitis A outbreak in a Roma (Gipsies) community (2004-2005), and 22 from patients with acute HAV from sporadic cases (2005-2006). A sample of CSF involved in a case of meningitis was also included. IgM anti-HAV detection and nested reverse transcription (RT-PCR), with primers located at the VP1-P2a region, was undertaken to detect HAV genome. In positive samples, molecular characterization was followed by phylogenetic analysis. All samples (n = 31) were positive for IgM anti-HAV. HAV RNA was found in 96.7% of cases. All isolates were classified as genotype I: 22 belonged to sub-genotype IA (73.3%), and 8 to sub-genotype IB (26.7%). All strains obtained from an acute HAV outbreak had sub-genotype IA, in which seven isolates (87.5%) had identical sequences. In HAV sporadic cases sub-genotypes IA and IB were identified, and this may reflect the co-circulation of these two sub-genotypes in Portugal. Molecular epidemiology of HAV infection in this group of Portuguese appears to be similar to other European countries. HAV phylogenetic studies can provide important information for the design of appropriate public health measures.

[Cervix uteri lesions and human papiloma virus infection (HPV): detection and characterization of DNA/HPV using PCR (polymerase chain reaction]. / Lesões do colo uterino e infecção pelo vírus do papiloma humano (HPV) detecção e tipificação do ADN/HPV por PCR (reacção de amplificação enzimática).

The prevalence of human papillomavirus (HPV) genotypes was estimated by the polymerase chain reaction (PCR), in archival paraffin was embedded tissues. The case group consisted of 84 women aged 21-67 years (mean, 40 years) who were referred to the Department of Gynaecology (Oncology Centre, Coimbra) with citopathologically abnormal smears. This group was selected from a population of women who had undergone a screening programme (1990/94) in Central Region of Portugal. All these patients (n = 84) had a colposcopic directed cervical biopsy. HPV detection and typing was performed by the PCR method in the Department of Virology (National Health Care Institute, Lisbon). The prevalence of DNA/HPV found, concerning all epithelial cervical lesions studied and classified as squamous intra-epithelial lesions (SIL) and cervical cancer was 97.8%. On the basis of the data presented in this study, it was estimated that there was a statistically significant prevalence of low risk HPV types (HPV 6/11) in low grade SIL, 83.3%, and a statistically significant prevalence of high risk HPV types (HPV 16,18,31,33,51) in high grade SIL, 58.4%, as well as cervical cancer lesions in 100%. We conclude that there was a statistically significant difference between women with low and high grade SIL for HPV infection, with low and high risk HPV types, respectively. The risk factors for cervical cancer investigated (age at first sexual intercourse, multiple sexual partners, parity, use of oral contraceptives) were not associated to statistically significant differences concerning low grade SIL and high grade SIL. The clinical and therapeutic procedures were evaluated for the same five years (1990/94). It may be concluded that there would be no significant difference in clinical procedure for high grade lesions and cervical cancer, in which the treatment had been frequently radical (cone biopsies, simple or radical hysterectomy) and in which the HPV infection persisted frequently and was associated to high risk types (HPV 16 in 50% of these cases). On the other hand, it may be concluded that HPV detection in cervical biopsies, especially for low grade SIL lesions, which were evaluated in this study with a more conservative procedure (clinical evaluation only, punch biopsies, loop diathermy, CO2 laser vaporisation, cone biopsies), could identify women with high risk HPV types who might be at risk of developing dysplasia and cervical cancer.

[Typing of human papillomavirus (HPV) in the male and female genitalia]. / Estudo do tipo de papilomavírus humano (HPV) no aparelho genital feminino e masculino.

Diagnosis and typing of HPV was started in November 1990 at the Virology department of the National Health Institute, Lisbon. Eighty one samples from 70 patients were studied, 57 from women observed at the cervico-vulvar out patient unit of the Gynecology department of Sta Maria Hospital, Lisbon, and 13 from male contacts of some of these women. Forty nine women (86%) had colposcopic, histological or cytological evidence of HPV infection. Eleven men (85%) have clinical signs of infection and 2 (15%) had had sexual intercourse with infected partners with clinical evidence of infection. HPV DNA was detected in 43 patients (61%). Forty two were infected with HPV 6/11 (98%) and one with HPV 16 (2%). These preliminary results suggest that genital infection by HPV must also be considered a public health problem in the field of sexually transmitted diseases in Portugal.